Structural diversity-guided optimization of carbazole derivatives as potential cytotoxic agents

Zilin Gao; Yu Chen; Yufei Nie; Keming Chen; Xiufang Cao; Shaoyong Ke

doi:10.3389/fchem.2023.1104868

Structural diversity-guided optimization of carbazole derivatives as potential cytotoxic agents

Front Chem. 2023 Jan 18:11:1104868. doi: 10.3389/fchem.2023.1104868. eCollection 2023.

Authors

Zilin Gao^{1

2}, Yu Chen¹, Yufei Nie¹, Keming Chen¹, Xiufang Cao¹, Shaoyong Ke²

Affiliations

¹ College of Science, Huazhong Agricultural University, Wuhan, China.
² National Biopesticide Engineering Research Centre, Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Sciences, Wuhan, China.

Abstract

Carbazole alkaloids, as an important class of natural products, have been widely reported to have extensive biological activities. Based on our previous three-component reaction to construct carbazole scaffolds, we introduced a methylene group to provide a rotatable bond, and designed series of carbazole derivatives with structural diversity including carbazole amide, carbazole hydrazide and carbazole hydrazone. All synthesized carbazole derivatives were evaluated for their in vitro cytotoxic activity against 7901 (gastric adenocarcinoma), A875 (human melanoma) and MARC145 (African green monkey kidney) cell lines. The preliminary results indicated that compound 14a exhibited high inhibitory activities on 7901 and A875 cancer cells with the lowest IC₅₀ of 11.8 ± 1.26 and 9.77 ± 8.32 μM, respectively, which might be the new lead compound for discovery of novel carbazole-type anticancer agents.

Keywords: SARs; anticancer; biological evaluation; carbazole derivatives; synthesis.

Grants and funding

This work was financially supported by the Natural Science Foundation of Hubei Province (2022CFB244), and the National Innovation and Entrepreneurship Training Program for College Students (202210504083).